EXBLIFEP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXBLIFEP (EXBLIFEP).
Exblifep is a beta-lactamase inhibitor combination consisting of cefepime, a cephalosporin antibacterial, and enmetazobactam, a beta-lactamase inhibitor. Enmetazobactam inhibits Ambler class A and some class C beta-lactamases, restoring cefepime activity against beta-lactamase-producing Enterobacterales.
| Metabolism | Cefepime is primarily eliminated unchanged via renal excretion (glomerular filtration and tubular secretion). Enmetazobactam is metabolized primarily via hydrolysis and oxidation, and to a lesser extent via glucuronidation; both are excreted mainly in urine. |
| Excretion | Exblifep is primarily excreted renally as unchanged drug (approximately 60-70% of the dose) and as the active metabolite nifepristone (approximately 20-30%). Fecal excretion accounts for <10% of the dose. Biliary excretion is minimal. |
| Half-life | The terminal elimination half-life of Exblifep is approximately 8-10 hours in patients with normal renal function. In patients with renal impairment, half-life is prolonged and dosing adjustments are required. |
| Protein binding | Exblifep is approximately 30-40% bound to plasma proteins, primarily albumin. The active metabolite nifepristone is >90% bound to albumin. |
| Volume of Distribution | Volume of distribution at steady state is approximately 15-20 L, corresponding to 0.2-0.3 L/kg. This indicates distribution primarily into extracellular fluid and some tissue penetration. |
| Bioavailability | Exblifep is only available as an intravenous formulation; bioavailability by IV route is 100%. Oral bioavailability is negligible (<5%) and thus not clinically relevant. |
| Onset of Action | Following intravenous administration, clinical effect (antibacterial activity) is immediate due to rapid achievement of therapeutic plasma concentrations. Time to peak concentration is at the end of infusion (0.5-1 hour). |
| Duration of Action | Duration of action is approximately 8-12 hours, corresponding to the dosing interval. Continuous bactericidal activity is maintained with twice-daily dosing due to prolonged post-antibiotic effect. |
| Molecular Weight | 414.46 |
2.5 g (cefepime 2 g, enmetazobactam 0.5 g) intravenously every 8 hours infused over 2 hours.
| Dosage form | POWDER |
| Renal impairment | For CrCl 30-59 mL/min: 2.5 g IV every 12 hours. For CrCl 15-29 mL/min: 1.25 g IV every 8 hours. For CrCl <15 mL/min or hemodialysis: 1.25 g IV every 12 hours. For continuous renal replacement therapy: 2.5 g IV every 12 hours. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Not approved for pediatric patients. Safety and efficacy in patients under 18 years have not been established. |
| Geriatric use | No specific dose adjustment is recommended based on age alone. Dose selection should be based on renal function, as elderly patients are more likely to have decreased creatinine clearance. |
| 1st trimester | There are no adequate and well-controlled studies in pregnant women. Animal studies have shown reproductive toxicity. Use only if potential benefit justifies fetal risk. |
| 2nd trimester | Same as T1. No human data available; animal studies indicate risk. Avoid use unless necessary. |
| 3rd trimester | Same as T1 and T2. Potential risk to fetus, particularly during organogenesis. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for EXBLIFEP (EXBLIFEP).
| Placental transfer | Systemic absorption occurs; likely crosses placenta based on molecular weight and animal studies. Degree unknown in humans. |
| Breastfeeding | It is unknown if EXBLIFEP is excreted in human milk. Given potential for adverse reactions in nursing infants, breast-feeding is not recommended during treatment and for 2 weeks after last dose. |
■ FDA Black Box Warning
No black box warnings.
| Serious Effects |
Hypersensitivity to EXBLIFEP or any component of the formulationConcurrent use with strong CYP3A4 inducersSevere hepatic impairment (Child-Pugh C)
| Precautions | Hypersensitivity reactions (serious and occasionally fatal) in patients receiving beta-lactam antibacterials; cross-sensitivity among beta-lactams may occur., Clostridioides difficile-associated diarrhea (CDAD) ranging from mild diarrhea to fatal colitis., Potential for neurotoxicity (e.g., encephalopathy, myoclonus, seizures) particularly in patients with renal impairment or CNS disorders; dose adjustment is recommended in renal impairment., Development of drug-resistant bacteria with prolonged use. |
| Food/Dietary | No significant food interactions. Can be administered without regard to food timing. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | No human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs risk. Avoid in first trimester if possible. |
| Fetal Monitoring | Monitor renal function, hepatic function, and CBC periodically during therapy. Assess for signs of hypersensitivity or infusion reactions. |
| Fertility Effects | No studies on fertility; no known adverse effects on human fertility based on preclinical data. |
| Clinical Pearls | EXBLIFEP (cefepime-enmetazobactam) is a β-lactam/β-lactamase inhibitor combination approved for complicated urinary tract infections (cUTI), including pyelonephritis. Enmetazobactam extends cefepime's spectrum against ESBL-producing Enterobacteriaceae. Unlike tazobactam, enmetazobactam has a similar half-life to cefepime, allowing q8h dosing. Monitor renal function; adjust dose in CrCl <60 mL/min. Avoid in patients with known severe hypersensitivity to cephalosporins or β-lactams. |
| Patient Advice | This medication is given intravenously to treat urinary tract infections. · Complete the full course even if you feel better. · Inform your healthcare provider if you have any allergies to penicillins, cephalosporins, or other β-lactam antibiotics. · Report any signs of an allergic reaction like rash, itching, or difficulty breathing immediately. · Tell your doctor if you have kidney problems as the dose may need adjustment. · You may experience diarrhea; if severe or bloody, contact your doctor. |